Effect of propylene glycol on the skin penetration of drugs
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Propylene glycol (PG) has been used in formulations as a co-solvent and/or to enhance drug permeation through the skin from topical preparations. Two skin in vitro permeation approaches are used to determine the effect of PG on drug penetration. The in vitro Skin-PAMPA was performed using 24 actives applied in aqueous buffer or PG. PG modulates permeability by increasing or diminishing it in the compounds with poor or high permeability, respectively. Percutaneous absorption using pigskin on Franz diffusion cells was performed on seven actives and their commercial formulations. The commercial formulations evaluated tend to have a lower permeability than their corresponding PG solutions but maintain the compound distribution in the different strata: stratum corneum, epidermis and dermis. The results indicate the enhancer properties of PG for all compounds, especially for the hydrophilic ones. Additionally, the Synchrotron-Based Fourier Transform Infrared microspectroscopy technique is applied to study the penetration of PG and the molecular changes that the vehicle may promote in the different skin layers. Results showed an increase of the areas under the curve indicating the higher amount of lipids in the deeper layers and altering the lipidic order of the bilayer structure to a more disordered lipid structure.
KeywordsPropylene glycol Percutaneous absorption PAMPA Franz cells µFTIR
The present work could not be performed without the important collaboration and contribution of Isabel Yuste and Service of Dermocosmetic Assessment from IQAC-CSIC. The authors are also grateful to Monserrat Rigol and Núria Solanes from the Department of Cardiology (Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) Hospital Clínic, Universitat de Barcelona, Spain) for supplying the porcine skin biopsies. Moreover, the work carried out in the synchrotron ALBA was possible thanks to the valuable help of M. Kreuzer and I. Yousef and the grant received from the Consortium for the Construction, Equipping and Exploitation of the Synchoton Light Sources (CELLS).
This work was partially funded by the Spanish Ministry of Economy and Competitiveness, project code RTC-2014-1901-1.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Animal handling was approved by the Institutional Review Board and Ethics Committee of Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. The management of the Landrace Large White pigs used in this study conforms to the Guide for the Care and Use of Laboratory Animals published by the United States National Institutes of Health (Eighth Edition. Washington, DC: The National Academies Press, 2011).
This study did not require formal informed consent.
- 7.Manca ML, Castangia I, Matricardi P, Lampis S, Fernàndez-Busquets X, Fadda AM, Manconi M (2014) Molecular arrangements and interconnected bilayer formation induced by alcohol or polyalcohol in phospholipid vesicles. Colloids Surf B Biointerfaces 117:360–367. https://doi.org/10.1016/j.colsurfb.2014.03.010 CrossRefPubMedGoogle Scholar
- 22.Manca ML, Matricardi P, Cencetti C, Peris JE, Melis V, Carbone C, Escribano E, Zaru M, Fadda AM, Manconi M (2016) Combination of argan oil and phospholipids for the development of an effective liposome-like formulation able to improve skin hydration and allantoin dermal delivery. Int J Pharm 505:204–211. https://doi.org/10.1016/j.ijpharm.2016.04.008 CrossRefPubMedGoogle Scholar
- 26.Hoang KT (1992) Dermal exposure assessment : principles and applications. U.S. Environmental Protection Agency, Office of Health and Environmental Assessment, Washington, DC, EPA/600/8-91/011BGoogle Scholar
- 28.Wester RC, Melendres J, Sedik L, Maibach H, Riviere JE (1998) Percutaneous absorption of salicylic acid, theophylline, 2, 4-dimethylamine, diethyl hexyl phthalic acid, and p-aminobenzoic acid in the isolated perfused porcine skin flap compared to man in vivo. Toxicol Appl Pharmacol 151:159–165. https://doi.org/10.1006/taap.1998.8434 CrossRefPubMedGoogle Scholar
- 32.Guidance document for the conduct of skin absorption studies. OECD Series on Testing and assessment, 2004; No. 28: 1–31, https://doi.org/10.1787/9789264078796-en
- 33.European Commission the SCCS Notes of Guidance for the Testing of Cosmetic Ingredients (2016) SCCS 1564. 151, https://doi.org/doi:10.2772/47128
- 34.Schaefer H, Redelmeier TE (1996) Skin barrier: principles of percutaneous absorption. Karger, BaselGoogle Scholar
- 37.Benseny-Cases N, Álvarez-Marimon E, Castillo-Michel H, Cotte M, Falcon C, Cladera J (2018) Synchrotron-based Fourier transform infrared microspectroscopy (μFTIR) study on the effect of Alzheimer’s Aβ amorphous and fibrillar aggregates on PC12 cells. Anal Chem 90:2772–2779. https://doi.org/10.1021/acs.analchem.7b04818 CrossRefGoogle Scholar
- 38.AS, CAMO SOFTWARE. https://www.camo.com/downloads/user-manuals.html. Accessed 20 Nov 2018
- 40.Alonso C, Carrer V, Espinosa S, Zanuy M, Córdoba M, Vidal B, Domínguez MJ, Godessart N, Coderch L, Pont M (2019) Prediction of the skin permeability of topical drugs using in silico and in vitro models. Eur J Pharm Sci 136:104945. https://doi.org/10.1016/j.ejps.2019.05.023 CrossRefPubMedGoogle Scholar
- 46.van Smeden J, Bouwstra JA (2016) Stratum corneum lipids: their role for the skin barrier function in healthy subjects and atopic dermatitis patients. In: Agner T (eds), Skin barrier function. Curr Probl Dermatol. Basel, Karger 49:8–26. https://doi.org/10.1159/000441540
- 48.Moghadam SH, Saliaj E, Wettig SD, Dong C, Ivanova MV, Huzi JTL, Foldvari M (2013) Effect of chemical permeation enhancers on stratum corneum barrier lipid organizational structure and interferon alpha permeability. Mol Pharm 10:2248–2260. https://doi.org/10.1021/mp300441c CrossRefPubMedGoogle Scholar
- 50.Barry BW, Bennett SL (1987) Effect of penetration enhancers on the permeation of mannitol, hydrocortisone and progesterone through human skin. J Pharm Pharmacol 39:535–546. https://doi.org/10.1111/j.2042-7158.1987.tb03173.x CrossRefPubMedGoogle Scholar